Free Desmosine is a Sensitive Marker of Smoke-Induced Emphysema.

Abstract

While the elastin-specific crosslinks, desmosine and isodesmosine (DID), are increased in blood, urine, and sputum of patients with clinically documented pulmonary emphysema, the usefulness of DID in detecting early lung injury remains untested. To this end, our laboratory has measured DID in a hamster model of smoke-induced emphysema, involving only minimal alveolar wall damage. Animals were either treated with cigarette smoke for 2h/day, 5 days/week, or exposed only to room air (controls) for a period of 3months. DID levels in bronchoalveolar lavage fluid (BALF) and whole lungs were determined at monthly intervals, using liquid chromatography and tandem mass spectrometry. Lung surface area was also determined, as a measure of airspace enlargement. The portion of BALF DID not bound to peptides (free DID) was significantly higher in smoke-exposed animals at 2months (9.2 vs 4.4pg/mg protein; p < 0.05), whereas total BALF DID showed no significant increases over the course of the study, and total lung DID remained unchanged. There was a mild, but significant, loss of lung surface area in the smoke-exposed group at 2months (28.8% vs 25.2%, p < 0.05), which showed no further progression, consistent with the return of free DID to control levels at 3months. These findings support the hypothesis that free DID are sensitive indicators of smoke-induced lung injury. Measurement of free DID in smokers with minimally decreased lung mass may help determine the utility of this parameter as a test for incipient pulmonary emphysema.